Use of Eltrombopag after Romiplostim in Primary ITP Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2790-2790
Author(s):  
Tomás José González-López ◽  
Cristina Pascual ◽  
María Teresa Álvarez-Román ◽  
Fernando Fernández-Fuentes ◽  
Blanca Sánchez-González ◽  
...  
Keyword(s):  
Platelet Count ◽  
Side Effects ◽  
Complete Remission ◽  
Adverse Events ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Initial Response ◽  
Complete Response ◽  
Oral Drug ◽  
Initial Response Rate

Abstract Background: The trombopoietin receptor agonists (TRAs) romiplostim and eltrombopag are effective and safe in the treatment of chronic immune thrombocytopenia (ITP). However, when no response is achieved or when adverse events occur with one TRA the value of the sequential use of romiplostim and eltrombopag has not been clearly established. Here we have evaluated the efficacy and tolerance of using eltrombopag after romiplostim in ITP. Methods: Fifty-one primary ITP patients (aged 18 years or more) who had been sequentially treated first with romiplostim and then with eltrombopag in the Spanish Eltrombopag Registry were retrospectively evaluated. In accordance with the usual standards, complete response was defined as a platelet count of 100x109/L and a response as a platelet count of 30x109/L or a count of at least twice the initial (pre-treatment) value. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age of our cohort was 49 [range, 18–83] years. There were 32 women and 19 men. According to the standard definition, patients were allocated to newly diagnosed (n=2), persistent (n=5) and chronic (n=44) ITP groups. The median number of therapies prior to administration of eltrombopag was 4 [range, 2–9], including splenectomy (39%), rituximab (33%) and romiplostim (100%). The median duration of romiplostim use before switching to eltrombopag was 12 (IQR 5–21) months. The reasons for switching from the romiplostim to eltrombopag were: lack of efficacy of romiplostim (n=25), patient's preference (n=16), platelet-count fluctuation (n=6), and side-effects (n=4). The initial response rate to eltrombopag was 41/51 (80.5%), including 67% (n=34) of cases with complete remission. After a median follow-up of 13 months with eltrombopag, 39 patients maintained their response. When eltrombopag was used for patients who were refractory to the maximum romiplostim dose the initial response rate of eltrombopag was 25%. However, 83% of patients who relapsed after their initial response to romiplostim responded to eltrombopag. Sixteen romiplostim responders requested their physicians to switch them to eltrombopag because they preferred an oral drug. The efficacy was maintained after switching in all 16 patients. In the platelet-count fluctuation group, the initial response rate was also 100%. All 4 patients who were switched to eltrombopag because they experienced side-effects of romiplostim achieved complete remission with eltrombopag and their adverse events were resolved. 16 / 51 (33%) patients experienced one or more adverse event during treatment with eltrombopag. The frequency of grade 3–4 adverse events during treatment with eltrombopag was 9.8%. Conclusion: The use of eltrombopag after romiplostim for treating ITP is effective and safe. The reason for discontinuing romiplostim was associated with the response to eltrombopag. Disclosures No relevant conflicts of interest to declare.

scholarly journals Extracorporeal Photopheresis for the Treatment of Mycosis Fungoides

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5062-5062 ◽  
Author(s):  
Erden Atilla ◽  
Pinar Ataca ◽  
Sinem Civriz Bozdag ◽  
Selami Kocak Toprak ◽  
Meltem Kurt Yuksel ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mycosis Fungoides ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Patient Characteristics ◽  
Complete Response ◽  
Ultraviolet B ◽  
Extracorporeal Photopheresis ◽  
Disease Extent ◽  
Topical Retinoids

Abstract Backround: The treatment of mycosis fungoides (MF) is determined by disease extent, prognostic factors and patient characteristics. Extracorporeal Photopheresis (ECP) was approved by the US Food and Drug Administiration for the palliative treatment of mycosis fungoides since 1988. Herein, we present our MF patients who have received ECP. Patients and Methods: We retrospectively included 50 MF patients who have diagnosed at our center. ECP was given empirically in cycles of 2 consecutive days in every 2 to 4 weeks at any time during their follow-up. Results: The patient characteristics is shown in table. Previous lines of treatments were; topical retinoids (bexarotene), topical corticosteroids, phototherapy (PUVA), Narrowband ultraviolet B light (NBUVB), Interferons, Metotrexate (MTX), CHOP (cyclophosphamide, daunorubicin, vincristine, prednisolone). ECP is combined with gemcitabine, PUVA, MTX, Bexaroten, IFN or Vorinostat. The overall response rate (ORR) was 54% with 30% complete response rate (CRR). 10/15 complete responders (67%) had stage 3-4 disease at diagnosis and 7/15 (47%) had received ≥ 3 lines of treatment prior to ECP. 18 patients (36%) had progressive disease after ECP while 3 patients (6%) were refractory and underwent allogeneic stem cell transplantation. The few adverse events of ECP included in 8 patients (16%) as catheter-related infection, headache, fever, chills and nausea. The OS was 68 months. Conclusion: ECP is a favorable treatment option for suitable patients in MF with high ORR and low risk of adverse events. Presenter has relevant financial relationship(s) to disclose: No. Disclosures No relevant conflicts of interest to declare.

Assessment of Response to Induction Therapy and Its Influence on 5-Year Failure-Free Survival in Group III Rhabdomyosarcoma: The Intergroup Rhabdomyosarcoma Study-IV Experience—A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group

2007 ◽  
Vol 25 (31) ◽  
pp. 4909-4913 ◽  
Author(s):  
Megan Burke ◽  
James R. Anderson ◽  
Simon C. Kao ◽  
David Rodeberg ◽  
Stephen J. Qualman ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Response Rate ◽  
Initial Response ◽  
Complete Response ◽  
Local Institutions ◽  
Protocol Violation ◽  
Free Survival ◽  
Entire Cohort ◽  
Group Iii

Purpose Initial response to induction chemotherapy predicts failure-free survival (FFS) in osteosarcoma and Ewing's sarcoma. For Intergroup Rhabdomyosarcoma Study (IRS) IV patients with group III rhabdomyosarcoma, we assessed whether reported response assessed by anatomic imaging at week 8 predicted FFS. Patients and Methods We studied 444 group III patients who received induction therapy, had response assessed at week 8 by anatomic imaging, and continued with protocol therapy. Induction chemotherapy was generally followed by radiation therapy (RT) starting after week 9. Response to induction therapy was determined at weeks 0 and 8. Local institutions coded response. Results Response rate for the entire cohort at week 8 was 77% (95% CI, 73% to 81%; complete response [CR], 21%; partial response [PR], 56%) but response had no influence on FFS (P = .57). Two hundred seventy-two patients received standard-timing RT at week 9 and thus only chemotherapy during induction. Response rate was 81% (95% CI, 76% to 86%; CR, 22%; PR, 59%). In these patients, response did not influence FFS except for those with alveolar histology. One hundred thirty-two other patients received chemotherapy and RT during induction (up-front RT). Response rate was 65% (95% CI, 57% to 73%; CR, 12%; PR, 53%), but response had no influence on FFS (P = .69). Forty patients received no RT at all (protocol violation) and response to induction therapy had no effect on FFS. Conclusion In IRS-IV, response rate to induction therapy was 77% in group III patients, was independent of histology, and had no influence on FFS overall.

scholarly journals Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia

2020 ◽  
Vol 38 (10) ◽  
pp. 1006-1018 ◽  
Author(s):  
Kim-Hien T. Dao ◽  
Jason Gotlib ◽  
Michael M.N. Deininger ◽  
Stephen T. Oh ◽  
Jorge E. Cortes ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Symptom Assessment ◽  
Complete Response ◽  
Serious Adverse Events ◽  
Chronic Neutrophilic Leukemia ◽  
Atypical Chronic Myeloid Leukemia ◽  
Grade 3

PURPOSE Colony-stimulating factor-3 receptor ( CSF3R)-T618I is a recurrent activating mutation in chronic neutrophilic leukemia (CNL) and to a lesser extent in atypical chronic myeloid leukemia (aCML) resulting in constitutive JAK-STAT signaling. We sought to evaluate safety and efficacy of the JAK1/2 inhibitor ruxolitinib in patients with CNL and aCML, irrespective of CSF3R mutation status. METHODS We conducted a phase II study of ruxolitinib in 44 patients (21 CNL and 23 aCML). The primary end point was overall hematologic response rate (ORR) by the end of 6 continuous 28-day cycles for the first 25 patients enrolled. We considered a response as either partial (PR) or complete response (CR). We expanded accrual to 44 patients to increase our ability to evaluate secondary end points, including grade ≥ 3 adverse events, spleen volume, symptom assessment, genetic correlates of response, and 2-year survival. RESULTS ORR was 32% for the first 25 enrolled patients (8 PR [7 CNL and 1 aCML]). In the larger cohort of 44 patients, 35% had a response (11 PR [9 CNL and 2 aCML] and 4 CR [CNL]), and 50% had oncogenic CSF3R mutations. The mean absolute allele burden reduction of CSF3R-T618I after 6 cycles was greatest in the CR group, compared with the PR and no response groups. The most common cause of death is due to disease progression. Grade ≥ 3 anemia and thrombocytopenia were observed in 34% and 14% of patients, respectively. No serious adverse events attributed to ruxolitinib were observed. CONCLUSION Ruxolitinib was well tolerated and demonstrated an estimated response rate of 32%. Patients with a diagnosis of CNL and/or harboring CSF3R-T618I were most likely to respond.

A Prospective, Randomized, Phase III Study of Melphalan 200 mg/m2 (MEL200) Versus Melphalan 100 mg/m2 (MEL100) in Newly Diagnosed Myeloma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 55-55 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Maria Teresa Petrucci ◽  
Antonietta Falcone ◽  
Anna Marina Liberati ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Phase Iii ◽  
Psychiatric Disease ◽  
High Dose ◽  
Free Survival ◽  
Grade 3

Abstract Several trials have shown the superior impact of high-dose melphalan (usually 200 mg/m2, MEL200) versus standard therapy in myeloma patients. Intermediate-dose melphalan (100 mg/m2, MEL100) was also superior to the standard dose, but MEL100 has not been clinically compared with MEL200 in a randomized study. In a case-matched study, response rate and event-free survival of MEL200 were superior to MEL100, but overall survival (OS) was similar. In this prospective, randomized, phase III trial, we compared the efficacy and toxicity of MEL200 and MEL100. Between January 2002 and July 2006, 299 patients were enrolled. Inclusion criteria were previously untreated myeloma, aged < 65 and Durie and Salmon stage II or III. Exclusion criteria were abnormal cardiac function, respiratory disease, abnormal liver function, abnormal renal function, HBV, HCV, or HIV positivity, concomitant cancer or psychiatric disease. The institutional review board approved the protocol and written informed consent was obtained from all patients. All patients received: 2 dexamethasone-doxorubicin-vincristine debulking courses (doxorubicin 50 mg/m2 day 1, vincristine 1 mg day 1, dexamethasone 40 mg days 1, 2, 3, 4, each course repeated every 28 days), 2 cycles of cyclophosphamide (4 g/m2, day 1) plus G-CSF followed by stem cell harvest. The MEL200 group was conditioned with 2 cycles of melphalan 200 mg/m2 followed by stem cell reinfusion; the MEL100 group was conditioned with 2 courses of melphalan 100 mg/m2 followed by stem cell reinfusion. At the present, 246 patients, median age 57 (range 32–65), completed the assigned therapy and were evaluated for response, progression-free survival (PFS) and OS. One-hundred and twenty-four patients were randomized to MEL200 and 122 to MEL100. Patient characteristics were similar in both groups. Abnormal cytogenetics (13q deletion, t(4;14), t(11;14), p53) were 75% in MEL200 patients and 56% in MEL100 patients (p=0.05). Forty-six patients did not complete tandem MEL200; 36 patients did not complete tandem MEL100. The near complete response rate of MEL200 was superior to MEL100 (32% versus 18%, p=0.011), but partial response was 80% versus 71%, respectively (p=0.079). The median follow-up for censored patients was 26.5 months. The 3 years PFS was 51% in the MEL200 arm and 33% in the MEL100 arm (HR=0.81, 95% CI 0.55–1.21, p=0.31). The 3 years OS was 86% in the MEL200 group and 71% in the MEL100 group (HR=0.82, 95 CI 0.45–1.48, p=0.51). Duration of grade 4 neutropenia and thrombocytopenia was comparable in two arms, but MEL200 patients required more platelet transfusions (p=0.03). Grade 3–4 non-hematological adverse events were reported in 49% of the MEL200 patients and in 38% of the MEL100 patients (P=0.07). The most frequent grade 3–4 adverse events were infections (54% of MEL200 patients versus 45% of MEL100 patients, p=0.25), mucositis (31% of MEL200 patients versus 7% of MEL100 patients, p=0.002) and gastrointestinal toxicities (20% of MEL200 patients versus 14% of MEL100 patients, p=0.3). In conclusion, MEL200 resulted in a significantly higher near complete response rate but this did not translate in a superior PFS and OS.

Bortezomib (Velcade ™) Observational Study in China: Efficacy and Safety of Bortezomib-Based Regimen in 395 Relapsed or Refractory Multiple Myeloma Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5179-5179
Author(s):  
Zhi-Xiang Shen ◽  
Hua Yan ◽  
Linna Wang
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Observational Study ◽  
Response Rate ◽  
Complete Response ◽  
Chinese Patients ◽  
Efficacy And Safety ◽  
Female Ratio ◽  
Bortezomib Treatment ◽  
Grade 3

Abstract Introduction: Multiple myeloma (MM) is a plasma-cell malignancy and overall survival for patients who have relapsed after initial therapy is approximately 2 years. Bortezomib (VELCADE TM) is a first-in-class proteasome inhibitor that has demonstrated significant anti-tumor activity in MM patients. Here we report the results of an observational study of the efficacy and safety of bortezomib-based regimens in Chinese relapsed/refractory MM patients. Methods: This was a multi-center, open-label, phase IV observational study designed to enroll 550 patients with relapsed or refractory MM. From Mar 2006 to May 2008, 500 patients with relapsed or refractory MM were enrolled from 43 medical centers in China and 395 of them were evaluated. Bortezomib (0.7 to 1.6 mg/m2 i.v.) was given on days 1, 4, 8, and 11 in in a 21-day cycle, up to a maximum of 8 cycles, combined with other agents, mainly with the addition of dexamethasone (60.1%). Major endpoint included response rate, safety and time to response. Responses of 62% patients were determined by European Group for Blood and Marrow Transplantation criteria (EBMT). Bortezomib withheld if patients developed neutropenia fever, grade 4 haematologic adverse events (AEs), or grade 3 non-haematologic AEs, and re-administered at 75% of the initial dosage after recovery. Results: In 395 evaluable cases, the median age was 59 years (range 35–82) and the male/female ratio was 1.5:1. 90% of patients were in late stage(stage II/III) and 50% of them were IgG subtype. Patients had received various prior therapies before bortezomib treatment, including VAD (31.3%), VBMCP (M2, 15.1%) and thalidomide-based regimens(14.9%), with best response rate of 10.4% complete response (CR) and 42.3% partial response (PR) from prior therapies. 311 (82%) cases of patients received 1.0–1.4mg/m2 bortezomib-based regimens treatment and 38.5% of them received at least 4 cycles of treatment. 364 patients were evaluable for response, the overall response rate was 287/364 (78.8%), 89 patients (24.5%) achieved a CR, 30(8.24%) had a nearly complete response (nCR), 168 (46.2%) had a PR, 39 (10.7%) had minimal response (MR), 24 (6.6%) had stable disease (SD), and the other 14 (3.9%) had progressive disease (PD). Median time to response was 1 cycle of treatment (range 1–6). Patients who received 4 or more cycles of bortezomib treatment achieved a higher response rate (CR+PR: 81.5%) compared to those who received fewer cycles (partly due to adverse events). And prognosis-related analysis showed that the dosage of bortezomib at 1.0 mg/m2 or more had a significant influence on the time to response and response rate, but no obvious effect on response duration, time to progress or the survival time. Drug related adverse events (AEs) were reported in 50.4% of patients during treatment, including hematologic AEs (mainly thrombocytopenia, 22.5%), gastrointestinal AEs (24.8%), and peripheral neuropathy (22.5%). The rates of grade 3–4 AEs of them were 46.1%, 11.2% and 15.7%, respectively. Serious AEs occurred in 33 (8.4%) cases and 23 (70%) patients recovered finally. Most AEs were predictable and manageable. Conclusion: Bortezomib-based regimen is effective treatment with higher response rate and is well tolerated in most Chinese patients with relapsed and refractory MM patients. Long-term follow-up is continuing.

Circularly Permuted TRAIL (CPT) combined with Thalidomide for the Treatment of Relapsed or Refractory Multiple Myeloma: An Open-Label, Multicenter Phase II Clinical Trial.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2958-2958 ◽  
Author(s):  
Wenming Chen ◽  
Jian Hou ◽  
Yaozhong Zhao ◽  
Lugui Qiu ◽  
Xiaoyan Ke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Phase Ii ◽  
Response Rate ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Phase Ii Studies ◽  
Better Than

Abstract Abstract 2958 Background: Circularly permuted TRAIL (CPT) is a recombinant mutant of human Apo2L/TRAIL developed by Beijing Sunbio Biotech Co. Ltd. as a targeted therapy for multiple myeloma and other hematologic malignancies. CPT is a dual pro-apoptotic receptor agonist that directly activates both pro-apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). CPT selectively induces apoptosis in a variety of cancer cells, while sparing most normal cells in preclinical models. Objective: CPT as a mono-therapy has shown definitive activities for patients with relapsed or refractory multiple myeloma (Rel/Ref MM) in phase I and phase II studies. The aim of this study is to observe the effect and safety of CPT in combination with thalidomide for Rel/Ref MM patients. Methods: In this multiple-center, open-label, single arm phase II study, 43 Rel/Ref MM patients who had received prior therapies and were resistant to thalidomide were recruited. These patients were divided into three groups, and received CPT 5.0mg/kg, 8.0mg/kg, and 10.0mg/kg on days1–5 of each 21-day cycle, respectively, until having finished six cycle‘s treatment or progression disease or intolerant adverse events. All the patients received thalidomide 100mg daily until to the disease progression or intolerant adverse events. Clinical responses of CPT were assessed by an independent review committee according to the criteria of the European Group for Blood and Marrow Transplantation (EBMT). Results: Among the 43 patients, 41 patients can be evaluated. There were 11, 15 and 15 patients in the three groups respectively. Among the 41 patients, two patients achieved complete response (CR), three showed near complete responses (nCR), four exhibited partial responses (PR), and five obtained minor responses (MR). The total response rates were 34% (including MR or better than MR), or 22% (including PR or better than PR). Among the three groups, the dose of 10mg/kg seemed to be optimal with 26.7% response rate (including PR or better than PR), superior to the other two groups. Duration of response of CPT was not evaluated accurately, because most patients who achieved PR, nCR, or CR were progression free at the end of the trial. The common treatment related adverse events (≥10%) were neutropenia, leucopoenia, fever, AST/ALT/LDH elevation, and thrombocytopenia. The grade 3 non-haematological toxicities were AST elevation (4.65%) and LDH elevation (2.33%). The elevation of AST and LDH seems to be related to tumor lysis, but not to liver injury. The grade 4 haematological toxicities were neutropenia and thrombocytopenia (2.33%, respectively) which might be related to thalidomide. Conclusions: The CPT combined with thalidomide was well-tolerated and an effective regimen for the treatment of Rel/Ref MM. The combination of CPT and thalidomide seems to be superior to CPT alone in CR/nCR response rate. Disclosures: Zheng: Beijing Sunbio Biotech Co., Ltd.: Employment. Zhu:Beijing Sunbio Biotech Co., Ltd.: Employment. Yang:Beijing Sunbio Biotech Co., Ltd.: Employment.

Bortezomib with Dexamethasone in Newly Diagnosed Patients with Primary Systemic Light Chain Amyloidosis or Multiple Myeloma-Associated AL Amyloidosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5036-5036 ◽  
Author(s):  
Beihui Huang ◽  
Juan Li ◽  
Junru Liu ◽  
Dong Zheng ◽  
Mei Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Side Effects ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Hematologic Response ◽  
Best Response ◽  
Organ Response

Abstract Abstract 5036 Objective: To assess the efficacy and tolerability of bortezomib with dexamethasone for patients with primary systemic light chain (AL) amyloidosis or multiple myeloma-associated AL amyloidosis. Methods: Twelve newly diagnosed patients with primary systemic AL amyloidosis and six patient with multiple myeloma-associated AL amyloidosis were treated with a combination of bortezomib (1. 3 mg/m2 d1, 4, 8, 11) and dexamethasone (20 mg d1–4). Results: Sixteen patients was evaluable. 12/16 had a hematologic response and 6/16 (37. 5%) a hematologic complete response. Median cycles to response was 1 cycle and median cycles to best response was 2 cycles. In patients with primary AL amyloidosis, 8/10 (80. 0%) had a hematologic response and 5/10 (50. 0%) a hematologic complete response. In patients with myeloma-associated AL amyloidosis, 7/10 (70. 0%) had a hematologic response and 1/6 (16. 7%) a hematologic complete response. Twelve patients (75. 0%) had a response in at least one affected organ, in which 7 in patients with primary AL amyloidosis and 5 in myeloma-associated AL amyloidosis. Person correlation between hematologic response and organ response was 0. 667 (p=0. 005). Fatigue, diarrhea and infection were the most frequent side effects. Three patients developed herpes zoster and had to stop chemotherapy. Conclusions: VD produces rapid and high hematological responses in the majority of patients with newly diagnosed AL regardless of primary or associated with myeloma. It is well tolerated with few side effects. This treatment may be a valid option as first-line treatment for newly diagnosed patients with primary systemic AL amyloidosis and multiple myeloma-associated AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

Single Agent Tamibarotene Has Activity in Acute Promyelocytic Leukemia Patients Previously Treated with ATRA and Arsenic Trioxide, but Does Not Produce Durable Responses

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3751-3751 ◽  
Author(s):  
David Sanford ◽  
Francesco LoCoco ◽  
Miguel A. Sanz ◽  
Eros Di Bona ◽  
Steven Coutre ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Complete Remission ◽  
Partial Response ◽  
Adverse Events ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Single Agent ◽  
Complete Response ◽  
Promyelocytic Leukemia ◽  
Cell Transplant

Abstract Background: Treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective as first-line therapy, although approximately 10% of patients relapse after treatment. Several mechanisms of ATRA resistance have been proposed including accelerated clearance of ATRA and increased levels of cellular retinoic acid-binding protein (CRABP), which induces retinoic acid metabolism. Tamibarotene is a synthetic retinoid that does not significantly bind CRABP, suggesting that it might be effective in APL patients with ATRA resistance. Tamibarotene has shown efficacy in APL patients with relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA Methods: We conducted a multicenter phase II clinical trial of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (concomitant or sequential). Participants were treated with single agent tamibarotene at a daily dose of 6 mg/m2 for up to 56 days during induction. Patients achieving a complete response were eligible to continue on consolidation treatment with tamibarotene at the same dose for a maximum of six 28 day cycles. The primary outcome for this trial was to determine the rate of durable complete response (CR) using tamibarotene as a single agent. Secondary outcomes included the rate of morphologic complete remission, partial response, cytogenetic complete response, molecular complete response as well as the safety profile and tolerability of this medication. Results: We enrolled 14 patients from March 2008 to October 2011 at 8 centers. The median age of the participants was 56 years (range 20-76). Twelve patients had relapsed APL and 2 had primary refractory disease. Patients had a median of 2 remissions (range 1-5) prior to enrollment with a median time from the most recent remission to study screening of 23 months (range 2-102). Twelve patients (86%) had received other treatments including stem cell transplant (n=4) in addition to ATO and ATRA prior to enrollment. Eight patients achieved a morphologic remission during treatment with tamibarotene and 2 had a partial response (>50% reduction in BM blasts). Three (21%) patients with complete morphologic remission had a CR, whereas 5 (36%) had a complete remission with incomplete hematologic recovery (CRi), without meeting pre-specified recovery of neutrophil (>1,000/μL) and platelet counts (>100,000/μL). Seven out of 8 patients who achieved CR or CRi relapsed after treatment. The median duration of response for patients achieving CR was 203 days (range 183-212). The median overall survival for the entire group was 233 days (95% CI 196-526 days). Thirteen patients reported treatment-emergent adverse events, although the majority were mild (Grade 1-2). The most frequently reported adverse events included rash (n=6, grade 1-3), headache (n=4, grade 1) and neutropenia (n=3, grade 3-4). Two patients experienced APL differentiation syndrome (grade 2). Two patients discontinued the study due to adverse events: one patient developed progressive multifocal leukoencephalopathy and the other developed pneumonia, although neither of these events was thought to be related to tamibarotene. Discussion: These results suggest that tamibarotene has activity in patients with relapsed APL after treatment with ATO and ATRA. Although the CR rate of 21% is lower than that reported in a previous trial using tamibarotene (58%; Tobita, 1997), the 24 patients in that study had received ATRA alone or in combination with chemotherapy, but not ATO. Thus, tamibarotene has significant clinical activity in this heavily pre-treated population with acceptable toxicity. Further studies using tamibarotene as initial therapy and in combination with ATO are warranted. Disclosures LoCoco: Lundbeck: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau. Cortes:CytRx: Research Funding.

scholarly journals Optimized duration of antituberculosis treatment for managing female genital tuberculosis: real-world experience from a high prevalence region in Eastern China

2020 ◽  
Author(s):  
Jian Sun ◽  
Wenjie Wang ◽  
Jing Ding ◽  
Yusheng Cheng ◽  
Yunfeng Zhou ◽  
...  
Keyword(s):  
Side Effects ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Single Side ◽  
Female Genital Tuberculosis ◽  
Group A ◽  
Intent To Treat ◽  
Group B ◽  
Female Genital

Abstract Background Duration of antituberculosis therapy (ATT) for managing female genital tuberculosis (FGTB) is controversial with the intermittent regimen no more advocated. We therefore conducted a prospective, real-world research to compare 6 months and 9 months of ATT.Methods Between 2012 and 2018, 109 drug-susceptible patients newly diagnosed with FGTB and/or tuberculous peritonitis (genital, 13; peritoneal, 34; mixed, 62) received naïve treatment for 9-12 months and further 18-month follow-up. Data on disease features at baseline and long-term outcome (intent-to-treat) were compared between group A (aged 18-35 yr) and group B (aged 36-81 yr). Efficacy and side effects of treatment were compared within each group 6 months and 9 months from ATT initiation (per-protocol), respectively. Results In contrast to group B at baseline, group A had more clinical evidence predicting active tuberculosis (P < 0.05), severer performance of genital lesions and pelvic adhensions (P < 0.05), more signs of active pulmonary tuberculosis (P < 0.01), and less performance of only TBP (P < 0.01). Intent-to-treat analysis showed higher incidence of overall single side effects and poor compliance in group B (P < 0.05), and similar recurrence rate between 2 groups. Per-protocol analysis showed increased complete response rate (P < 0.01) and similar incidence of side effects (P > 0.05) in group A, similar complete response rate (P > 0.05) and increased incidence of overall single side effects (P < 0.05) in group B at 9-month duration.Conclusions Younger females with FGTB had a greater risk of systemic infection of tuberculosis compared to older ones. Nine-month ATT using daily therapy proved to be beneficial for younger patients at reproductive age. Six-month option was suitable for older patients for reducing side effects and poor compliance in the duration of treatment.

scholarly journals Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Yali Tao ◽  
Hui Zhou ◽  
Ting Niu
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Response Rate ◽  
Complete Response Rate ◽  
Meta Analysis ◽  
Complete Response ◽  
Cochrane Central Register ◽  
Safety And Efficacy ◽  
Grade 3

Background: Selinexor (SEL) is an orally bioavailable, highly-selective, and slowly-reversible small molecule that inhibits Exportin 1. Preclinical studies showed that SEL had synergistic antimyeloma activity with glucocorticoids, proteasome inhibitors (PIs) and immunomodulators. The combination of selinexor and dexamethasone (DEX) has been approved in the United States for patients with penta-refractory multiple myeloma in July 2019. This meta-analysis aimed to investigate the safety and efficacy of selinexor based treatment in Multiple myeloma.Methods: We systematically searched the Medline (PubMed), Embase, Web of Science, Cochrane Central Register of Controlled Trials Library databases and ClinicalTrials.gov. Outcome measures of efficacy included overall response rate (ORR), clinical benefit rate (CBR), stringent complete response rate (sCR), complete response rate (CR), very good partial response (VGPR), partial response rate (PR), minimal response (MR), rate of stable disease (SDR), rate of progressive disease (PDR) and median progression-free survival (mPFS). Safety was evaluated by the incidences of all grade adverse events and Grade≥3 adverse events. The subgroup analysis was conducted to analyze the difference in different combination treatment regimens (SEL + DEX + PIs vs SEL + DEX).Results: We included six studies with 477 patients. The pooled ORR, CBR, sCR, CR, VGPR, PR, MR, SDR, and PDR were 43% (18–67%), 55% (32–78%), 5% (−2–13%), 7% (4–11%), 14% (5–24%), 23% (15–31%), 11% (8–14%), 26% (14–38%) and 14% (4–23%), respectively. SEL + DEX + PIs treatment had higher ORR (54 vs 24%, p = 0.01), CBR (66 vs 37%, p = 0.01), sCR (10 vs 2%, p = 0.0008), and VGPR (23 vs 5%, p &lt; 0.00001) compared to SEL + DEX treatment, and lower PDR (4 vs 23%, p &lt; 0.00001) and SDR (17 vs 37%, p = 0.0006). The pooled incidences of any grade and grade≥3 were 45 and 30% in hematological AEs, and in non-hematological AEs were 40 and 30%, respectively. The most common all grade (68%) and grade≥3 (54%) hematological AE were both thrombocytopenia. Fatigue was the most common all grade (62%) and grade≥3 (16%) non-hematological AE. Compared to SEL + DEX treatment, SEL + DEX + PIs treatment had lower incidences of hyponatremia (39 vs 12%, p &lt; 0.00001), nausea (72 vs 52%, p &lt; 0.00001), vomiting (41 vs 23%, p &lt; 0.0001), and weight loss (42 vs 17%, p = 0.03) in all grade AEs. Meanwhile, SEL + DEX + PIs treatment had lower incidences of anemia (36 vs 16%, p = 0.02), fatigue (20 vs 13%, p = 0.04), hyponatremia (22 vs 5%, p &lt; 0.0001) than SEL + DEX treatment in grade≥3 AEs.Conclusion: Our meta-analysis revealed that selinexor-based regimens could offer reasonable efficacy and tolerable adverse events in patients with multiple myeloma. SEL + DEX + PIs treatments had higher efficacy and lower toxicities than SEL + DEX.

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